The Effect of Age and Duration of Disease on Airway Structure in Fatal Asthma

Abstract

We hypothesized that if airway remodeling is related to duration of asthma, that when matched for severity, the airways of older adults should show greater alterations than the airways of younger adults. Using standard morphometric techniques, we compared airways with basement membrane perimeters (Pbm) between 2 and 10 mm from young individuals who died of asthma (n = 14, range 17-23 yr), and older individuals with fatal asthma (n = 13, range 40-49 yr). Comparisons were also made with normal airways from age-matched adults. Wall area was increased in old individuals with fatal asthma compared with young individuals with fatal asthma, primarily due to greater adventitial area, whereas wall area in young individuals with fatal asthma was not different from control subjects. Within muscle bundles the connective tissue matrix was increased around individual cells in individuals with asthma, unrelated to age. After adjustment for this change, smooth muscle area in both asthma groups was still greater than in age-matched control subjects, in old individuals with fatal asthma 4-fold greater (p = 0.04), and in young individuals with fatal asthma 2-fold greater (p = 0.03). Airway narrowing was increased in old versus young individuals with fatal asthma, with both groups more narrowed than control subjects. Intralumenal obstruction and subepithelial collagen in the two asthma groups were significantly greater than in control subjects, but there was no age effect. These data provide support for the hypothesis that there is an increase in airway wall area, including smooth muscle, and airway narrowing with increasing duration of severe asthma or with older age. The observation that total wall thickness was not greater in young individuals with young fatal asthma than in control subjects suggests that factors other than airway wall geometry contribute to the pathogenesis of fatal attacks in this age group.

Cardiotrophin-1 alters airway smooth muscle structure and mechanical properties in airway explants

“…Basement membrane length and the subtended smooth muscle bundle area were traced on axial sections using the Bioquant (BQ) system software (R&M Biometrics, Nashville, TN), as previously described, at a final magnification of ϫ250 (3,31). The proportion of smooth muscle in the wall sections was also quantified by projecting a computer-generated grid of points on the microscope field.…”

“…The area fraction of smooth muscle (Asm) in circumferential and axial sections was calculated as the number of points falling on muscle/total number of points on the wall at ϫ250 magnification. The proportions of muscle cells, cell nuclei, and extracellular matrix within muscle bundles were determined by point counting on both axial and circumferential sections at a final magnification of ϫ1,250, as previously described (3). Asm was calculated as: points falling on smooth muscle cells/total points within bundles multiplied by smooth muscle bundle points/total wall points at ϫ 250 (Asm bundle/wall).…”

“…These data indicate that CT-1 alters ASM structural and mechanical properties in the tissue environment and suggest that structural changes found in the airway wall in asthma are not necessarily associated with increased responsiveness. tracheal explants; mechanics; cytokines; asthma; matrix; smooth muscle hypertrophy INCREASED SMOOTH MUSCLE MASS has been repeatedly documented in asthmatic subjects (3,11,29,33,34), but the mechanisms responsible for the increased mass are unclear. The amount of both airway smooth muscle (ASM) and smooth muscle-associated matrix is greater with increased duration of asthma and may be an important determinant of the severity of airway responsiveness (3,15).…”

“…The amount of both airway smooth muscle (ASM) and smooth muscle-associated matrix is greater with increased duration of asthma and may be an important determinant of the severity of airway responsiveness (3,15). Yet the functional alterations in ASM in asthma are uncertain (29,34).…”

Remodelage bronchique dans l’asthme

“…Cependant, aucune relation linéaire n'a été démontrée tion semble cruciale pour déclencher l'expression clinique de l'asthme. Un contact environnemental délétère semble une piste sérieuse pour dater cette révélation asymptomatique [30].…”